Research over the past decade has provided convincing evidence for the existence of an endogenous analgesia system. The long term goal of the proposed research is a detailed description of the anatomical and pharmacological organization of descending brain stem input to the spinal trigeminal nucleus (STN) focusing on those projections arising from component nuclei of the endogenous analgesia system. The proposed three year investigation includes three specific aims designed to examine brain stem systems which may modulate nociceptive orofacial input to the STN. The specific aims are to: 1) Determine the afferent input to the STN; 2) Determine the sites of origin of enkephalin, substance-P, neurotensin, somatostatin and CCK-8 projections to the STN; and 3) Determine if cells projecting to the spinal trigeminal nucleus also project to the spinal cord or other brain regions. The methods used to accomplish these aims will include retrograde and anterograde tract tracing techniques, immunohistochemistry combined with retrograde tract tracing, and retrograde double labeling procedures. The research proposed here will provide new data on the organization of the endogenous analgesia system and its specific relationship to the spinal trigeminal nucleus. The information obtained from these studies will enhance our understanding of the mechanisms involved in brain stem modulation of incoming orofacial nociception and will provide novel information on the anatomy of the various neuropeptide systems which impinge on the spinal trigeminal nucleus.